855 resultados para DRUG-RESISTANCE GENE
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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
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Pós-graduação em Reabilitação Oral - FOAR
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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
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Leprosy is a chronic infectious condition caused by Mycobacterium leprae(M. leprae). It is endemic in many regions of the world and a public health problem in Brazil. Additionally, it presents a wide spectrum of clinical manifestations, which are dependent on the interaction between M. leprae and host, and are related to the degree of immunity to the bacillus. The diagnosis of this disease is a clinical one. However, in some situations laboratory exams are necessary to confirm the diagnosis of leprosy or classify its clinical form. This article aims to update dermatologists on leprosy, through a review of complementary laboratory techniques that can be employed for the diagnosis of leprosy, including Mitsuda intradermal reaction, skin smear microscopy, histopathology, serology, immunohistochemistry, polymerase chain reaction, imaging tests, electromyography, and blood tests. It also aims to explain standard multidrug therapy regimens, the treatment of reactions and resistant cases, immunotherapy with bacillus Calmette-Guérin (BCG) vaccine and chemoprophylaxis.
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Millions of people and animals suffer from superficial infections caused by a group of highly specialized filamentous fungi, the dermatophytes, which only infect keratinized structures. With the appearance of AIDS, the incidence of dermatophytosis has increased. Current drug therapy used for these infections is often toxic, long-term, and expensive and has limited effectiveness; therefore, the discovery of new anti dermatophytic compounds is a necessity. Natural products have been the most productive source for new drug development. This paper provides a brief review of the current literature regarding the presence of dermatophytes in immunocompromised patients, drug resistance to conventional treatments and new anti dermatophytic treatments.
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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Background: Next-generation sequencing (NGS) allows for sampling numerous viral variants from infected patients. This provides a novel opportunity to represent and study the mutational landscape of Hepatitis C Virus (HCV) within a single host.Results: Intra-host variants of the HCV E1/E2 region were extensively sampled from 58 chronically infected patients. After NGS error correction, the average number of reads and variants obtained from each sample were 3202 and 464, respectively. The distance between each pair of variants was calculated and networks were created for each patient, where each node is a variant and two nodes are connected by a link if the nucleotide distance between them is 1. The work focused on large components having > 5% of all reads, which in average account for 93.7% of all reads found in a patient. The distance between any two variants calculated over the component correlated strongly with nucleotide distances (r = 0.9499; p = 0.0001), a better correlation than the one obtained with Neighbour-Joining trees (r = 0.7624; p = 0.0001). In each patient, components were well separated, with the average distance between (6.53%) being 10 times greater than within each component (0.68%). The ratio of nonsynonymous to synonymous changes was calculated and some patients (6.9%) showed a mixture of networks under strong negative and positive selection. All components were robust to in silico stochastic sampling; even after randomly removing 85% of all reads, the largest connected component in the new subsample still involved 82.4% of remaining nodes. In vitro sampling showed that 93.02% of components present in the original sample were also found in experimental replicas, with 81.6% of reads found in both. When syringe-sharing transmission events were simulated, 91.2% of all simulated transmission events seeded all components present in the source.Conclusions: Most intra-host variants are organized into distinct single-mutation components that are: well separated from each other, represent genetic distances between viral variants, robust to sampling, reproducible and likely seeded during transmission events. Facilitated by NGS, large components offer a novel evolutionary framework for genetic analysis of intra-host viral populations and understanding transmission, immune escape and drug resistance.
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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Hepatitis C virus (HCV) infection represents an important public health problem worldwide. Reduction of HCV morbidity and mortality is a current challenge owned to several viral and host factors. Virus molecular evolution plays an important role in HCV transmission, disease progression and therapy outcome. The high degree of genetic heterogeneity characteristic of HCV is a key element for the rapid adaptation of the intrahost viral population to different selection pressures (e.g., host immune responses and antiviral therapy). HCV molecular evolution is shaped by different mechanisms including a high mutation rate, genetic bottlenecks, genetic drift, recombination, temporal variations and compartmentalization. These evolutionary processes constantly rearrange the composition of the HCV intrahost population in a staging manner. Remarkable advances in the understanding of the molecular mechanism controlling HCV replication have facilitated the development of a plethora of direct-acting antiviral agents against HCV. As a result, superior sustained viral responses have been attained. The rapidly evolving field of anti-HCV therapy is expected to broad its landscape even further with newer, more potent antivirals, bringing us one step closer to the interferon-free era. (C) 2014 Baishideng Publishing Group Inc. All rights reserved.
Immunomodulatory effects of low dose chemotherapy and perspectives of combanation with immunotherapy
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Nowadays cancer is one of the main causes of death and many efforts worldwide have been driven to find out new treatments and approaches in order to extinguish or reduce this group of disorder. Chemotherapy is the main treatment for cancer, however, conventional schedule based on maximum tolerated dose (MTD) show several side effects and frequently allow the development of drug resistance. In this review we present the evidence that metronomic chemotherapy, based on the frequent administration of low or intermediate doses of chemotherapeutics is as efficient as MTD and works better in some situations. Finally, we present some data indicating that noncytotoxic concentrations of antineoplastic agents are able to both up-regulate the immune system and increase the susceptibility of tumor cells to cytotoxic T lymphocytes. Taken together, data from the literature provide us the evidence that low concentrations of selected chemotherapeutics agents, rather than conventional high doses, should be chosen for combination with immunotherapy
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Pós-graduação em Medicina Veterinária - FCAV
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Pós-graduação em Odontologia - FOA
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Parasitism constitutes one of the main problems that affect livestock. Commercial acaricides have been used to control tick, but these chemicals have been responsible for the development of drug resistance and residues in the environment. Changes in the concept of production determined the search for natural measures, which guarantees animal sanity along with safety of the produced food. This assay had as objective to evaluate the citronella oil and neem oil in the control of bovine ticks. By the technique of adult ticks immersion, 280 ticks were evaluated, distributed in equal number throughout four treatments: negative control group, positive control (ivermectin), neem oil and citronella oil. It was analyzed the mortality index, estimated reproduction, product efficiency, index of eggs production and the hatchability rate. The efficiency of the product was verified by the mortality index just for the positive control group (100%) and citronella oil (97.14%). Also, the citronella oil inhibited the eclosion of eggs in 100%. The other treatments did not presented the minimum eclosion inhibition level of 95%. Under the conditions of the present assay citronella oil was efficient against Rhipicephalus (Boophilus) microplus. This result was not observed in relation to the neem oil.
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Parasitic diseases constitute one of the main problems affecting livestock; however the use of chemical medicaments provides drug resistance residues in animal and environmental contamination. Changes in production concepts require that food must be produced in hygienic conditions, per healthy animals and that are not eliminating antibiotic residues, pesticides or other drugs. This scenario has favored organic production and the use of medicinal plants. For the control of endoparasites, several studies have published the benefits of Azadirachta indica A. Juss., Punica granatum Linn., Musa sp., Operculina hamiltonii G. DON., propolis, among others. However, despite the existence in- vitro studies that demonstrate the pharmacological properties of phytotherapics, there is still need for clinical trials to determine dosage and its effects in- vivo. Investigations of new bioactive natural substances can be of great value for the control of animal health and food safety, which is particularly important for organic production systems in which the use of chemical drugs is a limiting factor for certification.
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)